Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.     

Avoidance of dental visits: the predictive validity of three dental anxiety scales

The purpose of this study was to determine the sensitivity, specificity, positive and negative predictive values for Corah's Dental Anxiety Scale (DAS) and two modified versions of it (MDAS; MDAS/4). A questionnaire was mailed to a simple random sample of 1,190 25-year-old residents in the west of Norway in 1997. Half the sample received DAS, the other half MDAS. The response rate after one reminder was 62%. The respondents completed the scales, gave demographic particulars and answered one question about dental visiting habits during the last 5 years plus an open-ended question about reasons for nonattendance. Using the answers to the latter question as validating criterion, it was found that, for all scales, sensitivity decreased while specificity improved when changing from a liberal to a stringent cut-off point. The scales gave low positive predictive values (≤0.26), but high negative predictive values (≥0.98). Since DAS and MDAS/4 gave almost identical findings, the two samples were combined. At a cut-off point ≥13 sensitivity was 0.83, specificity 0.84, positive predictive value 0.18 and negative predictive value 0.99. The corresponding estimates when the cut-off point was ≥15 were 0.67, 0.90, 0.22 and 0.98. It is concluded that, in this test, DAS and the two versions of MDAS gave acceptable, or near acceptable sensitivity, specificity and negative predictive values, but far too low positive predictive values to be useful for prediction at the individual level.     

Gene–environment interactions in the aetiology of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutathion S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.     

A novel computerized functional assessment for human immunodeficiency virus-associated neurocognitive disorder

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is present in 30–60 % of HIV-positive (HIV+) individuals and can be assessed by neuropsychological testing and level of functional impairment. HAND diagnosis therefore requires accurate assessment of functional impairment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a computer-based screening tool that includes performance-based measures of functional impairment. We sought to evaluate the CAMCI as a functional assessment tool in HAND. One hundred fourteen HIV+ patients and 38 HIV-negative (HIV?) patients underwent neuropsychological and CAMCI testing. Cognitive status for HIV+ subjects was classified using the Frascati criteria. HIV+ subjects grouped together and classified by cognitive impairment performed worse than HIV? subjects on several of the CAMCI tasks, including following directions to the supermarket (p?=?0.05, p?=?0.03), recalling which items to purchase (p?=?0.01, p?=?0.02), and remembering to stop at a supermarket (p?<?0.01, p?=?0.01) and the post office (p?<?0.01, p?=?0.03). After controlling for hepatitis C status and depression symptomatology, the tasks “following directions to the supermarket” and the “recalling which items to purchase” were no longer significant. The “remembering to run two separate errands” tasks retained their significance (p?<?0.01 for both tasks). A subset of the CAMCI tasks therefore successfully differentiated HIV+ patients from HIV? individuals. Differences in hepatitis C status and depression symptomatology could account for some of the function assessment differences in the CAMCI. These results suggest the CAMCI could be a useful objective performance-based functional assessment in patients with HIV.     

Apparent mineralocorticoid excess (AME) syndrome

Apparent mineralocorticoid excess (AME) syndrome is a rare autosomal recessive disorder due to the deficiency of 11β hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). Mutations in this gene affect the enzymatic activity resulting to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor leading to inherited hypertension. This is a potentially fatal but treatable disorder. We present clinical and molecular studies on two sisters diagnosed as AME.     

Clinical characteristics,molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015).

Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n?=?19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n?=?12), 35% for CD68 (n?=?8), 30% for CD34 (n?=?7), and 26% for lysozyme (n?=?6). Cytogenetic abnormalities were seen in 63% (n?=?12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n?=?3) or monosomal (n?=?2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p?=?0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p?Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.     

Caries decline before fluoride toothpaste was available: earlier and greater decline in the rural north than in southwestern Norway

The purpose of this study was to evaluate factors related to caries in 6–17-year-olds in 2 groups of Norwegian counties between 1966 and 1983. The average number of surfaces filled and permanent teeth extracted due to caries declined in the 4 northern counties from 1967. An increase was recorded in the 7 southwestern counties until 1971, then a decline. In the 1960s significantly more surfaces were filled and teeth extracted in the north compared to the southwest. Based on intra-county comparisons, the decline in surfaces treated was greater in the north between 1967 and 1983; 5.4 ± 0.4 vs 3.7 ± 0.7, P < 0.01. The averages were 1.9 surfaces treated in the north and the southwest in 1983. Higher infant mortality, lower percentage of people with completed senior secondary education, and more inhabitants per doctor and per dentist in the north indicate a less favorable situation than in the southwest. School-based fluoride programs had been implemented in both groups from the mid-1960s and around 60% participated when fluoride toothpaste became freely marketed in 1971. More fluoride programs and more fluoride tablets were available to children in the north; this may indicate a preventive attitude among dentists. The decline of caries started at different times in different parts of Norway. In the rural north with the most unfavorable situation, the decline was greater and started years before fluoride toothpaste came on to the market. The early decline may partly be ascribed to the school-based fluoride programs, the continued decline to several factors.